Method for measuring analysis object and measuring device

ABSTRACT

The measurement device comprises a sensor holder to which is removable to a biosensor. The sensor holder has measurement-use connection terminals that are in contact with the electrode system in the biosensor and are used to take off signals required for measuring the specific component, and thermocouple-use connection terminals that are in contact with the thermocouple in the biosensor and are used to take off the thermoelectromotive force signals.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to Japanese Patent Application No.2008-157259. The entire disclosures of Japanese Patent Application No.2008-157259 are hereby incorporated herein by reference.

BACKGROUND

1. Technical Field

The present invention relates to an analyzer for measuring a highlycontaminating/infectious analysis object, and more particularly relatesto an analyzer with a disposable sensor, and to a constitution andmeasurement method for providing high assay accuracy.

2. Description of the Prior Art

In the field of sensors, when the analysis object as a sample is asubstance of biological origin, this is specifically referred to asbiosensing, and analytical devices used for this are called biosensingdevices.

Biosensing devices include those in which the molecular recognitionability of microbes, enzymes, antibodies, and other such biomaterials isutilized among the measurement factors of a sensor that recognizes ananalysis object, and a biomaterial is used as a molecular identificationelement. Specifically, materials of biological origin are used to sendout signals proportional to concentration and the like, and so forth. Inparticular, we have seen the practical application of biosensors thatmake use of the immune response of antibodies or enzyme reactions, andthese biosensors are widely used in the medical field and in the foodsafety field. Qualitative and quantitative methods that have beendeveloped span a wide range, including electrochemical analysis andoptical analysis. Also, when a highly contaminating/infectious analysisobject is to be measured with a small sensing device, a disposablesensor is usually used in which the sensor portion that comes intocontact with the sample can be removed.

In particular, with analyzers in the medical field related to the healthof humans, when disposable sensors are used to prevent secondaryinfection, because of the important role of such devices, they need tohave high measurement accuracy. Accordingly, with biosensing devices inthe medical field, various corrections are made to the measured valuesfor the specific components in the analysis object in order to achievehigher measurement accuracy. For instance, there is temperaturecorrection, correction of measurement error due to similar substances,correction of interfering substances, and so forth, and when theanalysis object is blood, there is a special hematocrit valuecorrection. In turn, optimization of a calibration line and a sensor bylot management, and the like probably fall under the heading ofcorrection.

Temperature is an especially important factor since it affects allphysical and chemical reactions. For example, in the measurement of aspecific component in an analysis object, if the ambient measurementtemperature is higher than a reference temperature for which acalibration line has been set (although this does not applyunconditionally), there will be acceleration at various analysis(reaction) stages, and the measurement result will probably be greaterthan the actual true value, and if the temperature is lower than the setreference, the reverse may be true.

One commonly adopted method for solving this problem is to provide anenvironmental temperature sensor within the measurement device, selectthe value thereof as the temperature of the reaction region, and subjectthe specimen concentration value to temperature correction. This method,however, just involves artificially using the environmental temperatureas the ambient measurement temperature, so error will occur if there isdeviation between the temperature of the measurement component (or moreprecisely, the measurement region) and the environmental temperature.Particularly with extremely small measurement devices that are held inthe hand, a discrepancy from the actual environmental temperature tendsto occur when the device is warmed by the body heat of the user at thestage of preparing to measure.

In view of this, there has been a need for a way to measure and correctthe temperature of an analysis object measurement component to achievemore accurate temperature correction (see Patent Citations 1 and 2, forexample).

For instance, in Patent Citation 1 (Japanese Patent No. 3,595,315), theconstitutions shown in FIG. 13 a, which is an exploded diagram of asensor, and FIG. 13 b, which illustrates a measurement device in which asensor has been inserted, are discussed. A thermally conductive layer824 is provided to part of the sensor, and the temperature of themeasurement component is transferred to the end of the sensor insertedin the measurement device. The measurement device is equipped with atemperature sensor 832 that measures the temperature through directcontact with this thermally conductive layer, measures the amount ofheat transferred, and subjects the measured specific componentconcentration information to temperature correction.

In Patent Citation 2 (International Laid-Open Patent Application2003/062812 pamphlet), the constitution shown in FIG. 14, which is across section of the main components of a measurement device in which asensor is inserted, is discussed. A thermally conductive layer 912B isprovided to a sensor holder directly under the analysis objectmeasurement component of the sensor, the measurement device is furtherequipped with a temperature sensor 912A that comes into direct contactwith this layer, the transferred heat or the direct temperature of thesensor is measured, and the measured specific component concentrationinformation is subjected to temperature correction.

SUMMARY

Nevertheless, with the constitution discussed in Patent Citation 1 or 2,the temperature of the analysis object or the measurement component ismeasured indirectly, and direct measurement is impossible. Anotherproblem with the constitution discussed in Patent Citation 1 is that ifthe thermally conductive layer between the measurement component and thetemperature sensing unit comes into contact with a fingertip or othersuch thermal element that is different in temperature from that of theanalysis object, the accuracy of the measured temperature suffers.Moreover, since the temperature of the measurement device is, of course,also readily transferred to the thermally conductive layer, it wouldseem to be extremely difficult to accurately measure the temperature ofthe measurement region. Also, with the constitution discussed in PatentCitation 2, a temperature sensing unit is provided directly under themeasurement component. With this constitution, however, a sensorsubstrate is sandwiched in between, and the thermal conductivity of theplastic resins used for sensor substrates is generally extremely low.Consequently, even though a thermally conductive layer is installed onthe measurement device side, specific changes in the temperature of themeasurement region cannot be ascertained. Furthermore, it remainsuncertain whether accurate measurement is possible in a situation inwhich there is a substrate (an adiabatic material). Also, just as inPatent Citation 1, the effect of heat transferal to the measurementdevice side probably cannot be eliminated.

It is an object of the present invention to solve the above-mentionedproblems encountered in the past, and to provide an analysis objectmeasurement method, and a measurement device with which the effect oftemperature due to measurement conditions can be kept to an absoluteminimum, and a specific component of an analysis object can be measuredaccurately.

The analysis object measurement method pertaining to the presentinvention is a method for measuring an analysis object in which aspecific component in an analysis object is measured with a biosensorsystem comprising a holder for holding the analysis object, an electrodesystem for measuring the analysis object, and a thermocouple formed byjoining at least two dissimilar substances, said method comprising aspecimen measurement step, a temperature information computation step,and a temperature compensation step. In the specimen measurement step, aspecific component is measured in a spot of the analysis object that hasbeen applied to the holder. In the temperature information computationstep, temperature information is acquired using the thermocouple. In thetemperature compensation step, the value measured in the specimenmeasurement step is corrected on the basis of the temperatureinformation.

The measurement device pertaining to the present invention comprises asensor holder to which is removable to a biosensor. The sensor holderhas measurement-use connection terminals that are in contact with theelectrode system in the biosensor and are used to take off signalsrequired for measuring the specific component, and thermocouple-useconnection terminals that are in contact with the thermocouple in thebiosensor and are used to take off the thermoelectromotive forcesignals.

Also, an analyzer that realizes the present invention has a constitutioncomprising a thermocouple or an compensating lead wire thereof that isconnected to a thermocouple-use connection terminal within themeasurement device, and having a reference temperature/environmentaltemperature sensor that measures the temperature of the referencetemperature junction that is the end thereof, or has a constitution inwhich a thermocouple ends on a biosensor, having a reference temperaturejunction temperature sensor that measures the temperature of thereference temperature junction that is the end thereof in the sensorholder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified flowchart of the temperature-compensatinganalyzer pertaining to an embodiment of the present invention, and ofthe measurement algorithm in the method thereof;

FIG. 2 is a simplified diagram of the configuration of the analyzer inFIG. 1;

FIGS. 3 a, 3 b, and 3 c are simplified diagrams of the configuration ofthe sensor component in the temperature-compensating analyzer of thepresent invention;

FIG. 4 is a simplified diagram of the configuration of a measurementdevice in Embodiment 1 of the present invention;

FIGS. 5 a and 5 b are a simplified diagram of a temperature measurementsystem in Embodiment 1 of the present invention, a view of the statewhen the sensor is inserted, and a modification example of anenvironmental temperature sensor;

FIG. 6 is a simplified diagram of the measurement system steps inEmbodiment 1 of the present invention;

FIG. 7 is a simplified diagram of the measurement system steps inEmbodiment 1 of the present invention;

FIG. 8 is a graph of the relationship between temperature difference andthermoelectromotive force obtained in Embodiment 1 of the presentinvention;

FIG. 9 is a graph of the change over time in temperature information fora measuring junction, obtained in Embodiment 1 of the present invention;

FIG. 10 is a simplified diagram of an analyzer in Embodiment 2 of thepresent invention;

FIG. 11 is a simplified diagram of a measurement device in Embodiment 2of the present invention;

FIGS. 12 a, 12 b, and 12 c are a simplified diagram of the configurationof a temperature measurement system in Embodiment 2 of the presentinvention;

FIGS. 13 a and 13 b are an exploded view of a conventional sensor and asimplified diagram of a measurement device in which a sensor isinserted; and

FIG. 14 is a cross section of the main components of a measurementdevice in which a conventional sensor is inserted.

DETAILED DESCRIPTION

Embodiments of the temperature-compensating analyzer (biosensor system)and method thereof (method for measuring an analysis object) of thepresent invention will now be described in detail along with thedrawings.

Embodiment 1

The temperature-compensating analyzer and method thereof of Embodiment 1will now be described on the basis of FIGS. 1 to 9.

The case described here is a blood glucose sensor, in which blood isused as the analysis object and the glucose concentration (measuredvalue) is measured as the specific component. Naturally, FIGS. 1 to 9are merely embodiments of the present invention, and the invention isnot limited to or by these drawings.

FIG. 1 is a diagram of the overall algorithm when a blood glucose valuesensor (biosensor) 1 is mounted in a measurement device 2, and aspecific component concentration is then measured. FIG. 2 is asimplified diagram of the overall configuration of an analyzer(biosensor system) when the blood glucose value sensor 1 is mounted tothe measurement device 2.

Next, the blood glucose value sensor 1, which is a constituent elementof the analyzer and method of this embodiment, will be described indetail.

FIG. 3 is a representative exploded perspective view of the bloodglucose value sensor 1.

In this embodiment, the blood glucose value sensor 1 can be manufacturedby laminating a substrate (first substrate) 11, a spacer (thirdsubstrate) 13, and a cover (second substrate) 12 in that order andintegrating them.

There are no particular restrictions on the material of the substrate 11other than that it be insulating, but examples include polyethyleneterephthalate (PET), polyethylene naphthalate (PEN), polycarbonate (PC),polyimide (PI), polyethylene (PE), polypropylene (PP), polystyrene (PS),polyvinyl chloride (PVC), polyoxymethylene (POM), monomer cast nylon(MC), polybutylene terephthalate (PBT), methacrylic resin (PMMA), ABSresin (ABS), glass, and silicon substrates. Of these, polyethyleneterephthalate (PET), polyethylene naphthalate (PEN), polycarbonate (PC),and polyimide (PI) are preferable, and polyethylene terephthalate (PET)is particularly favorable. There are no particular restrictions on thesize of the substrate 11, but when it is in the form of a board asdepicted, for example, it may have an overall length of 5 to 100 mm, awidth of 3 to 50 mm, and a thickness of 0.05 to 2 mm, and preferablywill have an overall length of 10 to 70 mm, a width of 3 to 30 mm, and athickness of 0.1 to 1 mm, and more preferably will have an overalllength of 10 to 40 mm, a width of 5 to 10 mm, and a thickness of 0.1 to0.6 mm.

In this embodiment, there are no particular restrictions on the materialof the spacer 13 other than that it be insulating, but the samematerials as those listed for the substrate 11 can be used, for example.There are no particular restrictions on the size of the spacer 13, butwhen it is in the form depicted, for example, it may have an overalllength of 5 to 100 mm, a width of 3 to 50 mm, and a thickness of 0.01 to1 mm, and preferably will have an overall length of 10 to 70 mm, a widthof 3 to 40 mm, and a thickness of 0.05 to 0.5 mm, and more preferablywill have an overall length of 10 to 30 mm, a width of 5 to 10 mm, and athickness of 0.05 to 0.25 mm. A notch is formed in the spacer 13, whichwhen flanked by the substrate 11 and the cover 12 serves as a channelfor introducing an analysis object as a sample, and forms a cavity(holder) 17 for holding the analysis object. The size thereof isdetermined by the volume of the sample to be measured and by thethickness. The notch may be formed, for example, by cutting or piercingwith a laser, a die, or the like. Also, one of the substrates may beproduced in three-dimensional mold so as to form the cavity 17. In thiscase, a sensor may be formed by two substrates.

There are no particular restrictions on the material of the cover 12 inthis embodiment, and the same materials as those listed for thesubstrate 11 can be used, for example, but the material is preferablytransparent or semi-transparent so that the introduced sample will beeasy to see. Also, if an electrode is provided over the cover 12 asdiscussed below, the material must be insulating. Preferably, theportion of the cover 12 corresponding to the roof of the cavity 17 issubjected to a hydrophilic treatment. Examples of hydrophilic treatmentsinclude a coating with a surfactant, and introducing hydrophilicfunctional groups such as hydroxyl groups, carbonyl groups, or carboxylgroups, to the cover surface by plasma treatment or the like. There areno particular restrictions on the size of the cover 12, but if it hasthe shape depicted in the drawings, for example, it may have an overalllength of 5 to 100 mm, a width of 3 to 50 mm, and a thickness of 0.01 to0.5 mm, and preferably will have an overall length of 10 to 70 mm, awidth of 3 to 30 mm, and a thickness of 0.05 to 0.3 mm, and morepreferably will have an overall length of 10 to 40 mm, a width of 5 to10 mm, and a thickness of 0.05 to 0.2 mm. A hole 19 is preferably formedin the portion of the cover 12 corresponding to the roof of the cavity17. If the hole 19 is disposed at the distal end of the cavity 17, forexample, it may be a sample introduction hole for aiding theintroduction of sample, and if disposed on the inner side of the cavity17, it may be an air vent hole for taking the sample spot smoothly intothe cavity 17; thus the role played by the hole varies with where it isdisposed. Accordingly, its shape is not limited to being circular, andmay instead be elliptical, polyhedral, etc., and a plurality of holesmay also be provided. If there is a plurality of holes, the size andshape of each may be varied according to the intended role. The hole 19may be formed by cutting or piercing with a laser, a die, a drill, etc.Also, in the molding of the cover 12, the mold may be machined so as toallow the hole 19 to be formed.

Next, the integration method for laminating the substrate 11, the spacer13, and the cover 12 in that order may involve sticking the threemembers together with an adhesive agent, or may involve thermal fusionbonding. Examples of adhesives that can be used include epoxy adhesives,acrylic adhesives, polyurethane adhesives, thermosetting adhesives (hotmelt adhesives, etc.), UV curing adhesives, and so forth.

Next, the configuration of the blood glucose value sensor 1 in thisembodiment will be described. A measurement component 18 constituted bya measurement-use reagent 15 and an electrode system 14 for measuringthe glucose concentration in a sample is installed in the blood glucosevalue sensor 1, part of a thermocouple 16 that is a temperaturemeasurement circuit for obtaining temperature information about themeasurement component 18 is also installed, and a measuring junction 41at which are joined the wiring 16 a and 16 b made of the two differentmaterials of the thermocouples is installed near the measurementcomponent 18.

The two different materials of the thermocouples 16 a and 16 b arecomposed of a combination of metal, alloy, and semiconductor, anddepending on this combination, the measurement temperature range, theresistance to acidity and alkalinity, and the thermoelectromotive forcecharacteristics will exhibit various features. The manufacturing stepsand cost can be reduced by having one of the materials used for thethermocouples 16 a and 16 b be the same as the material of the electrodesystem 14.

The electrode system 14 consists of at least a working electrode and acounter electrode, and a reference electrode (not shown) may be providedas well. As for the types thereof, in addition to a measurementelectrode, it is often the case that a detection electrode (not shown)for detecting the introduction of a sample, or an electrode formeasuring various correction items is installed.

In the case of a blood glucose sensor, the measurement-use reagent 15includes glucose dehydrogenase or another such redox enzyme, andincludes as optional components a mediator, an enzyme stabilizer, areagent crystal homogenizer, an enzyme reaction stabilizer, or the like.This is usually disposed spanning the working electrode and the counterelectrode so as to facilitate electrochemical action between the twoelectrodes.

Upon being dissolved by the introduction of a sample, themeasurement-use reagent 15 undergoes a redox reaction with a specificcomponent contained in the analysis object. At this point, a specificvoltage is applied between the working electrode and the counterelectrode, which causes current proportional to the concentration of thespecific component to flow between the working electrode and the counterelectrode.

The voltage applied for measuring specimen concentration is, forexample, at least the voltage at which an electron transfer substanceincluding an enzyme or mediator contained in the measurement-use reagent15 will act with an electrode. This applied voltage is preferably 0.001to 2.0 V, and more preferably 0.05 to 1.0 V, and even more preferably0.1 to 0.6 V, when the specimen concentration measurement electrode is atwo-electrode type. If the specimen concentration measurement electrodeis a three-electrode type, the voltage is applied between the workingelectrode and the reference electrode, and the applied voltage is −0.5to 1.5 V, and more preferably −0.2 to 0.6 V, when the referenceelectrode is made of silver-silver chloride. Meanwhile, the applicationtime is, for example, 0.001 to 60 seconds, and more preferably 0.01 to10 seconds, and even more preferably 0.01 to 5 seconds.

The wiring between the electrode system 14 and the thermocouple 16 may,for example, be installed on the same substrate 11, as shown in FIG. 3a, or, as shown in FIG. 3 b, the wiring for the electrode system 14 maybe provided on the substrate 11 side, the wiring for the thermocouple 16provided on the cover 12 side, so that the wiring is installed onopposing faces of the substrate 11 and the cover 12 flanking themeasurement component 18. Furthermore, as shown in FIG. 3 c, theconstitution may be such that the wiring for the electrode system 14 isprovided on the substrate 11 side, the wiring for the thermocouple 16 isprovided on the spacer 13, and the measuring junction 41 is located onthe side face of the cavity 17. That is, the wiring for the thermocouple16 and the wiring for the electrode system 14 need not be provided onjust the substrate 11, and can be disposed on the cover 12 or the spacer13 as desired. Whatever the disposition, the measurement component 18,which is made up of the electrode system 14 and the measurement-usereagent 15, and the measuring junction 41, which is the junction of thethermocouples 16 a and 16 b constituted by joining wiring of twodissimilar materials, are both installed in the cavity 17 so as to comeinto direct contact with the analysis object that is introduced.

With the blood glucose value sensor 1, one method for installing thewiring for the electrode system 14 and the thermocouple 16 is to form athin film of the substance constituting the wiring over the entiresurface of the constituent member of the blood glucose value sensor 1 bysputtering, vapor deposition, or printing, using a metal, alloy,semiconductor, or the like as the material, and making slits in thisthin film with a laser, thereby creating a specific wiring pattern.However, as shown in FIG. 3 a, when the electrode system 14 and thethermocouple 16 are provided on the same substrate, it is necessary toform a thin film by mutually masking or otherwise treatment the portionswhere the electrode system 14 and the thermocouple 16 are formed fromdifferent materials. In this case, the junction of the thermocouples 16a and 16 b is preferably disposed on the distal end side of the cavity17, upstream from the electrode system 14. The advantage to this is thatthere is no need to worry about intersection with the detectionelectrode (not shown) that is part of the electrode system 14, whichmeans that the manufacturing process can be simplified.

The laser can be, for example, a YAG laser, a CO2 laser, a green laser,an excimer laser, etc. As an alternative method, the wiring may beformed in a restricted area in just a predetermined pattern by screenprinting. Or, in sputtering or vapor deposition, masking may beperformed just as with screen printing, and then a thin film electrodeand thermocouples may be formed in just a predetermined pattern. Thewiring pattern is not limited to just what is disclosed in the workingexamples and so forth, and there are no restrictions as long as theeffect of the present invention can be obtained.

The measurement device 2, which is a constituent element of thisembodiment, will now be described.

FIG. 4 is a detail enlargement of the portion where the blood glucosevalue sensor 1 is mounted to the measurement device 2. FIG. 5 a is anoblique view of the state before and after the mounting of the bloodglucose value sensor 1 to a sensor holder 3 that removably holds thesensor.

As shown in FIGS. 2, 4, and 5, the measurement device 2 constitutingthis embodiment comprises the sensor holder 3 that removably holds theblood glucose value sensor 1, which is a constituent element just as inthis embodiment, and on the inside thereof are installed measurement-useconnection terminals 31 and thermocouple-use connection terminals 32,which are respectively corresponding connection terminals for formingelectrochemical junctions with the electrode system 14 and thethermocouples 16 a and 16 b in the blood glucose value sensor. In otherwords, the ends of both the electrode system 14 and the thermocouples 16a and 16 b on the blood glucose value sensor 1 are disposed at locationsthat come into contact with the connection terminals 31 and 32.

With the measurement-use connection terminals 31, for example, voltageis applied, via a switching circuit, between a detection electrode fordetecting the introduction of an analysis object into the cavity 17, oran electrode for measuring the concentration of an analysis object, andan electrode for measuring various correction items. Various kinds ofinformation obtained as current values by measurement with the electrodesystem 14 and the thermocouples 16 a and 16 b is converted into voltagevia a current/voltage circuit, then converted into a digital signal andsent to an arithmetic processing unit 23. The various correction itemsreferred to here are, for example, hematocrit value correction,correction of interfering substances, etc. Naturally, these are justexamples, and all correction items that allow for electrochemicalmeasurement are encompassed, and if some metering function besideselectrochemical measurement is added to the measurement device 2 side,then that information is also encompassed.

The thermocouple-use connection terminals 32 are connected to secondwires (second thermocouples) 21 a and 21 b provided ahead of time to themeasurement device 2. The second wires 21 a and 21 b are made of thesame material as the thermocouples 16 a and 16 b on the blood glucosevalue sensor 1, or are compensating lead wires corresponding to therespective thermocouples. Since a characteristic of a thermocouple isthat the temperature difference at a junction where two dissimilarmaterials are joined is outputted as a thermoelectromotive force, it ispossible to compute the temperature difference between junctions, butthe temperature of the measuring junction 41 is not known. Accordingly,another junction (the ends of the second wires 21 a and 21 b in thisembodiment (see FIG. 5)) becomes a reference temperature junction 42,and the temperature difference can be measured as a voltage byconnecting a voltage gauge directly to these ends. The ends of thesecond wires 21 a and 21 b, as discussed above, are the referencetemperature junction 42 in a biosensor/measurement device integratedtype of thermocouple that is integrated with a sensor. Thus, the twoneed to be disposed as close as possible, so that there will be notemperature difference between the ends. The distance between the endsis preferably no more than 10 mm, and more preferably no more than 5 mm,and even more preferably no more than 3 mm.

The role of the thermocouple-use connection terminals 32 is to connectthe thermocouples 16 a and 16 b on the blood glucose value sensor 1, orthe second wires 21 a and 21 b in the measurement device 2, and are eachmade of the same material as the respective thermocouples, or areconstituted by compensating lead wires corresponding to the respectivethermocouples. The surface of the thermocouple-use connection terminals32 may also be plated to make them more durable when plugged in and outof the blood glucose value sensor 1, as terminals that also have thefunction of holding the blood glucose value sensor 1. Alternatively, ifthe design makes use of a structure or material that will produce aslittle temperature difference as possible between the ends and thedistal ends of the connection terminals, there will be no problem at allwith using a material that is different from that of the thermocouples,because of the thermocouple characteristics. For instance, if a materialwith extremely high thermal conductivity is used, then the temperatureat the ends and the distal ends of short connection terminals will besubstantially uniform.

As discussed above, a characteristic of a thermocouple is that thetemperature difference at a junction where two dissimilar materials arejoined is outputted as a thermoelectromotive force, it is possible tocompute the temperature difference between junctions, but thetemperature of the measuring junction 41 is not known. Accordingly, itis necessary to measure the temperature of the reference temperaturejunction 42 and measure a reference temperature. Thus, with themeasurement device 2 that is a constituent element in this embodiment,an environmental temperature sensor 22 that measures the environmentaltemperature is installed at the ends of the second wires 21 a and 21 b,that is, at the reference temperature junction 42, or nearby, and withthis structure the temperature is the same at said ends and theenvironmental temperature sensor 22. Nevertheless, the environmentaltemperature sensor 22 has two purposes: the function of measuring theenvironmental temperature, and the function of measuring the referencetemperature of the thermocouples. Examples of the environmentaltemperature sensor 22 include a thermistor, a temperature measuringresistor, an IC temperature sensor, and a radiation thermometer.

Also, as shown in FIG. 5 b, for example, the environmental temperaturesensor 22 may comprise a first temperature sensor 22 a for acquiring thereference temperature of the thermocouples, and a second temperaturesensor 22 b for acquiring the environmental temperature of themeasurement device 2, with these two being provided separately.

Using the blood glucose value sensor 1 and the measurement device 2 iswhat affords the effect of the present invention. Specifically, when thethermocouples 16 a and 16 b are installed in the blood glucose valuesensor 1 and the second wires (may be compensating lead wires on themeasurement device side, as mentioned above) 21 a and 21 b are installedin the measurement device 2, and when, as shown in FIG. 5, the bloodglucose value sensor 1 is mounted to the sensor holder 3 that removablyholds the blood glucose value sensor 1, the thermocouples 16 a and 16 band the second wires 21 a and 21 b are linked via the thermocouple-useconnection terminals 32 in the sensor holder 3, forming abiosensor/measurement device integrated type of thermocouple. In theblood glucose value sensor 1, the measuring junction 41, which is thedistal ends of the thermocouples 16 a and 16 b, is disposed in thecavity 17 where level of the analysis object is measured, and in themeasurement device 2, a pair of thermocouples is formed in which theends of the second wires 21 a and 21 b serve as the referencetemperature junction 42, and the environmental temperature sensor 22disposed near the reference temperature junction 42 measures thereference temperature. Consequently, the result is a thermocoupleanalyzer in which the blood glucose value sensor 1 and the measurementdevice 2 are integrated. Thus, a thermoelectromotive force is generatedif there is a temperature difference between the measuring junction 41of the thermocouples 16 a and 16 b, which are in the form of anintegrated thermocouple via the thermocouple-use connection terminals32, and the reference temperature junction 42, which is the ends of thesecond wires 21 a and 21 b. This thermoelectromotive force is amplifiedby an amplifying circuit provided as needed, that information isconverted into a digital signal by an A/D converting circuit via aswitching circuit, and information about a temperature differencebetween the measuring junction 41 and the reference temperature junction42 is transmitted to the arithmetic processing unit 23.

FIGS. 6 and 7 are simplified diagrams of the various measurement stepsand arithmetic processing in this temperature-compensating thermocoupleanalyzer. A simplified diagram of the various measurement steps andarithmetic processing was divided into FIGS. 6 and 7, but it should benoted that this is only to make it easier to understand the temperaturecompensation step S9 in the arithmetic component, and steps performed atthe same time are shown as being divided.

If there is a temperature difference between the measuring junction 41and the reference temperature junction 42 disposed as above, athermoelectromotive force is outputted according to this temperaturedifference. A temperature information computation step S5 in which theenvironmental temperature and the measuring junction temperature aredetermined is then performed by means of a temperature differencemeasurement step S2 in which this thermoelectromotive force is measured,an environmental temperature measurement step S3 involving the use ofthe environmental temperature sensor 22, and a measuring junctiontemperature calculation step S4 in which the measuring junctiontemperature is calculated from the temperature difference informationobtained in the temperature difference measurement step S2 and using theenvironmental temperature as a reference temperature. On the basis ofthe temperature information thus obtained, temperature compensation isperformed for various correction items other than temperature and theanalysis object concentration obtained in the specimen concentrationmeasurement step (specimen measurement step) S1 discussed below.

Blood glucose value measurement using an analyzer with a temperaturecompensation function is carried out as follows, which is describedaccording to the algorithm in FIG. 1, for example.

First, when the blood glucose value sensor 1 is placed in a dedicatedmeasurement device 2, the system awaits sample introduction, andchecking for sample introduction is begun. Meanwhile, the user pierces afingertip or the like with a dedicated lancet or the like to draw blood.This blood is brought into contact with a blood supply opening at thedistal end of the cavity 17 of the blood glucose value sensor 1 placedin the measurement device 2, and capillary action or assistance from asurfactant causes the blood to be introduced into the cavity 17.

The specimen concentration measurement step S1 is commenced when thedetection electrode (not shown) that is part of the electrode system 14detects that the required amount of blood has been introduced into thecavity 17. When the blood is introduced into the cavity 17, themeasurement-use reagent 15 is dissolved, and a redox reaction beginswith the glucose in the blood and an enzyme that uses glucose as asubstrate. Here, when voltage is applied to the measurement electrode,which is part of the electrode system 14, current corresponding to theglucose concentration flows to the measurement electrode system 14. Thespecimen concentration measurement step S1 is performed in which thecurrent value thus obtained is converted by a circuit into voltage, thenconverted into a digital signal, and converted by the arithmeticprocessing unit 23 into glucose concentration information, and thisconcentration information is stored in a memory device 24. Measurementis usually also performed for the various correction itemssimultaneously with or immediately before and after the specimenconcentration measurement step S1. The environmental temperaturemeasurement step S3 is then performed in which the environmentaltemperature information measured simultaneously with or before or afterthe measurement of the specimen is transferred from the environmentaltemperature sensor 22 to the arithmetic processing unit 23 and theenvironmental temperature is calculated.

The temperature difference measurement step S2 is also performedsimultaneously with the specimen concentration measurement step S1.Specifically, the change in the thermoelectromotive force due to thetemperature difference between the measuring junction 41 and thereference temperature junction 42 is measured, information about thechange in temperature difference per unit of time for the two junctions,or information about the temperature difference within a specific lengthof time or at a certain point in time, is converted into a digitalsignal by the various circuits, and information about the temperaturedifference from the reference temperature junction is calculated by thearithmetic processing unit 23. Then, the measuring junction temperaturecalculation step S4 is performed by the arithmetic processing unit 23,in which the environmental temperature obtained in the environmentaltemperature measurement step S3 and stored in the memory device 24 isused as a reference temperature, and the temperature of the measuringjunction 41 is calculated by matching this with the temperaturedifference information obtained in the temperature differencemeasurement step S2.

As discussed above, the obtained analysis object concentrationinformation and measurement information for the various correction itemsundergo correction by temperature information. Specifically, theanalysis object concentration information is subjected to theenvironmental temperature compensation step S6, in which correction isperformed by the arithmetic processing unit 23 according to theenvironmental temperature information, and to the measuring junctiontemperature compensation step S7, in which correction is performedaccording to the measuring junction temperature information, andcorrection is also performed for the various correction items at asuitable timing before or after this. Naturally, as to these correctionitems that are affected by temperature, as shown in FIG. 7, accuracy canbe further improved by performing the correction item temperaturecompensation step S8 in which temperature correction is performed byusing environmental temperature information and measuring junctiontemperature information.

The glucose concentration is ultimately displayed on a display component25, after the various corrections including temperature.

Next, a blood glucose value sensor in which a thermocouple 16 was formedwith the configuration shown in FIG. 3 a was actually produced, and therelationship between the temperature difference between the measuringjunction 41 and the reference temperature junction 42, and thethermoelectromotive force produced at the sensor/measurement deviceintegrated thermocouple was measured with changing environmentaltemperature, the results of which are given in FIG. 8. The horizontalaxis is the difference in the thermoelectromotive force with respect toa reference voltage of approximately 3.26 V, and the vertical axis isthe temperature difference between the measuring junction 41 and thereference temperature junction 42 corresponding to thethermoelectromotive force. The term “reference voltage” here means thevoltage applied ahead of time to a voltage measurement device to amplifyand measure the negative thermoelectromotive force generated underconditions that the measuring junction 41 is lower than the referencetemperature junction 42. In this embodiment, it can be seen that when avalue under the reference voltage of 3.26 V was indicated, a negativethermoelectromotive force equivalent to this difference was generated.That is, the temperature of the measurement component must be lower thanthat of the reference temperature junction.

Measurement was conducted indoors at a constant temperature, with threedifferent environmental temperature conditions employed: around 25° C.,30° C., and 35° C. As to the temperature of the sample, three spots wereprepared so that the temperature would be constant near 20° C., 25° C.,and 30° C., and measurements were made at the respective environmentaltemperatures.

As a result, as shown in FIG. 8, when the environmental temperature isheld steady at 20° C., as the temperature of the sample is changed from20° C. to 25° C. and then 30° C., the thermoelectromotive forcegenerated at the thermocouple is −3.5 mV, 11.5 mV, and 26.5 mV,respectively, and when the environmental temperature is held steady at25° C., as the temperature of the sample is changed from 20° C. to 25°C. and then 30° C., the thermoelectromotive force generated at thethermocouple is −15.5 mV, −2.5 mV, and 10 mV, respectively, and when theenvironmental temperature is held steady at 30° C., as the temperatureof the sample is changed from 20° C. to 25° C. and then 30° C., thethermoelectromotive force generated at the thermocouple is −30.5 mV, −17mV, and −3.5 mV, respectively. It is clear from these results that apositive thermoelectromotive force is generated with respect to thereference voltage if the temperature of the measuring junction 41 ishigh with respect to the reference temperature junction 42, andconversely, if the temperature is low, a negative thermoelectromotiveforce is outputted.

Also, as shown in FIG. 8, it can be seen that an approximation line forresults under all conditions maintains linearity at all environmentaltemperatures, with R2=0.9974. That is, no matter what the environmentaltemperature is, the relationship between the thermoelectromotive forceand the temperature difference is obtained as data in a linearrelationship approximated by a linear expression. The fact that this isobtained as a linear expression in which the calibration line is linearis extremely advantageous in the temperature difference measurement stepS2 in which the temperature difference between the reference temperaturejunction 42 and the measuring junction 41 is calculated on the basis ofthe generated thermoelectromotive force. That is, with the integratedanalyzer comprising the blood glucose value sensor 1 and the measurementdevice 2 in this Embodiment 1, no matter what the measurementenvironmental temperature, the value of the temperature differencebetween the two junctions can be computed with a single calibration lineand without variance.

More specifically, when this data is stored as a calibration line in thememory device 24, then in the temperature difference measurement step S2the obtained thermoelectromotive force can be converted into informationabout the temperature difference between the reference temperaturejunction 42 and the measuring junction 41 without being affected by theenvironmental temperature. The temperature difference informationobtained in this way in the temperature difference measurement step S2is further subjected to the measuring junction temperature calculationstep S4, in which it is added up by the arithmetic processing unit 23using the environmental temperature obtained in the environmentaltemperature measurement step S3 as a reference, so that the temperatureof the measuring junction 41 is computed.

Then, on the basis of the measuring junction temperature information andthe environmental temperature information thus obtained, the temperaturecompensation step S9 is performed, in which the correspondingenvironmental temperature compensation-use correction table or measuringjunction temperature compensation-use correction table which isprospectively stored is referred to and, if correction is necessary, theanalysis object concentration is subjected to temperature compensation.The temperature compensation step S9 also includes the correction itemtemperature compensation step S8 in which the various correction itemsare also subjected to temperature compensation.

Here, naturally, depending on the conditions of the temperaturecompensation, the compensation can be performed in both theenvironmental temperature compensation step S6 based on theenvironmental temperature and the measuring junction temperaturecompensation step S7 based on the measuring junction temperature, orjust with temperature information from one or the other.

In the measuring junction temperature compensation step S7 based on themeasuring junction temperature, measuring junction temperatureinformation can be obtained as information about the temperature changein the measurement component 18 over time during measurement, and thetemperature changes due to all internal and external thermal factorsthat affect the temperature of the measurement component 18 can bedetected in real time. Of course, it is also possible to detect changesin the temperature of the measurement component linked to thetemperature of the specimen when the specimen is introduced, or the peaktemperature of the measurement component.

FIG. 9 is a graph of the measured values obtained by monitoring thechange in thermoelectromotive force when a specimen whose temperature ishigher than the environmental temperature is introduced into the cavity17 for a while after the blood glucose value sensor 1 has been insertedinto the measurement device 2 constituted as in this embodiment. Thehorizontal axis is the time elapsed since the blood glucose value sensor1 was mounted in the measurement device 2, and the vertical axis is thethermoelectromotive force related to the temperature difference betweenthe reference temperature junction 42 and the measuring junction 41.This shows the change over time in thermoelectromotive force related tothe temperature difference between the measuring junction and thereference temperature junction.

As a result, as shown in FIG. 9, when the blood glucose value sensor 1that has been stored indoors at an environmental temperature of 20° C.is inserted into the measurement device 2, the detectedthermoelectromotive force is higher than the reference voltage, butgradually tapers off. This is because when the blood glucose valuesensor 1 is taken out of its stored case and mounted in the measurementdevice 2, the fingertips come into contact with the blood glucose valuesensor 1 and the heat of the fingertips is transferred to the bloodglucose value sensor 1, so that the temperature of the measuringjunction 41 of the blood glucose value sensor 1 is higher than theenvironmental temperature of the measurement device 2. The effect offingertip temperature is also affected by the environmental temperaturewhere the blood glucose value sensor 1 and the measurement device 2 arethemselves stored.

After this, the thermoelectromotive force steadily drops, and afterabout 40 seconds have elapsed the voltage holds steady at about 3.262 V,but this means that since the reference voltage of the thermocouple isapproximately 3.26 V in the prototype used in this embodiment, thevoltage is the same as the reference voltage, that is, the temperatureof the measuring junction 41 of the blood glucose value sensor 1conforms to the temperature of the environment, until there is no longerany difference from the environmental temperature of the measurementdevice 2. Thus, in this embodiment, the difference between thetemperature of the measuring junction 41, which indicates thetemperature of the measurement component, and the reference temperature,which indicates the environmental temperature, can be detected in realtime.

Next, a spot of 30° C. sample, which was 10° C. higher than theenvironmental temperature of 20° C., was placed in the cavity 17 of theblood glucose value sensor 1 about 80 seconds after the start ofmeasurement. As a result, the detected value for thermoelectromotiveforce rose sharply to approximately 3.28 V. The peak of this temperaturerise is calculated from the calibration line shown in FIG. 8 and foundto be approximately 7° C., which is lower than the temperature of theapplied specimen. The reason for this is surmised to be that the totalamount of sample is too small with respect to the thermal capacity hadby the blood glucose value sensor 1 or the environmental temperature, sothe heat is absorbed before the measurement component 18 rises to thetemperature of the specimen.

After the peak temperature rise has been reached, the temperature of themeasurement component 18 gradually approaches the environmentaltemperature, just as with the fingertip temperature.

As shown in FIGS. 2, 3, and 5, with this embodiment, it probably can beunderstood that the specimen temperature can be measured directly bydisposing the measuring junction 41 in the cavity 17. Also, due to highresponse speed of the thermocouple, it can be seen that the change intemperature around the measurement component 18 can be measured in realtime by measuring the temperature in parallel with concentrationmeasurement.

Naturally, the measuring junction temperature information used in themeasuring junction temperature compensation step S7 does not require allof the change in temperature of the measurement component 18 over thecourse of measurement to be measured if the embodiment is optimized.That is, if the temperature change pattern of the measurement component18 after specimen introduction, or the time over which it is possible toaccurately detect the peak measurement component temperature isthoroughly scrutinized, then measurement may be performed for just aslong as required after the start of measurement. Moreover, thetemperature difference measurement step S2 can be concluded by obtainingmeasurement component temperature information for just a certain pointin time after the start of measurement.

Thus, accurate temperature compensation of an analysis object can beachieved, which was impossible with conventional environmentaltemperature compensation alone. Therefore, this embodiment makes itpossible to accomplish accurate measurement in which the effect ontemperature by measurement conditions is kept to a minimum.

Also, the data for the prototype in Embodiment 1, namely, thethermocouple that is used, the resistance thereof, the amount ofamplification by the amplifier, the thermoelectromotive force, and thelinearity of the calibration line obtained from this, will vary greatly,so it should be noted again that the calibration line obtained here isnothing but one aspect of Embodiment 1.

Embodiment 2

Next, the temperature-compensating analyzer (measurement device) andmethod thereof (method for measuring an analysis object) of Embodiment 2will be described through reference to FIGS. 10 to 12. Those elementsthat are the same as in Embodiment 1 will be numbered the same, and willbe treated as being included in Embodiment 2 as well. FIGS. 10 to 12 areof course nothing more than an aspect of the present invention, and thisembodiment is not limited to or by these.

As shown in FIGS. 10, 11, and 12, an integrated temperature-compensatingthermocouple analyzer comprising the blood glucose value sensor 1 andthe measurement device 2 in Embodiment 2 differs from Embodiment 1 inthe configuration of the thermocouple, the position of the referencetemperature junction 42, and the configuration of the environmentaltemperature sensor 22 that measures the reference temperature.

In Embodiment 2, the thermocouple, which is part of a temperaturecorrecting circuit, ends only on the blood glucose value sensor 1, andthe second wires 21 a and 21 b disposed in the measurement device 2 inEmbodiment 1 are omitted. At the same time, the material of thethermocouple-use connection terminals 32 disposed in the sensor holder 3that removably holds the blood glucose value sensor 1 is different fromthe material of the thermocouple. Accordingly, in Embodiment 2, the endsof the thermocouples 16 a and 16 b on the blood glucose value sensor 1act as a reference temperature junction 43, and if there is atemperature difference between this reference temperature junction 43and the measuring junction 41, a thermoelectromotive force is generatedbetween the ends of the thermocouples 16 a and 16 b. That is, asdiscussed above, the thermocouple ends at just the thermocouples 16 aand 16 b on the blood glucose value sensor 1.

In addition, as shown in FIGS. 12 a and 12 b, the environmentaltemperature sensor 22 is incorporated as a reference temperaturejunction sensor 33, and is incorporated so as to come into contact withthe reference temperature junction 43 (or nearby it) on the mountedblood glucose value sensor 1 inside the sensor holder 3 that removablyholds the blood glucose value sensor 1, with this contact being eitherdirect or indirect via the provision of a thermally conductive layer 34,and this sensor measures the temperature of the reference temperaturejunction 43. Examples of reference temperature junction sensor 33include a thermistor, a temperature sensing resistor, an IC temperaturesensor, and a radiation thermometer.

As shown in FIG. 12 c, for example, the reference temperature junctionsensor 33 may comprise a third temperature sensor 33 a for acquiring thereference temperature of the thermocouples, and a fourth temperaturesensor 33 b for acquiring the environmental temperature of themeasurement device 2, with these two being provided separately.

In this case, in a preferable configuration, as shown in FIG. 12 b, thethermally conductive layer 34 is provided to afford indirect contact.This creates a structure in which the reference temperature junctionsensor 33 is enveloped by the thermally conductive layer 34, so thetemperature of the reference temperature junction 43 is transferred morequickly, and also serves to protect the reference temperature junctionsensor 33 from the physical effect of inserting and removing the bloodglucose value sensor 1.

There are no particular restrictions on the material of the thermallyconductive layer 34, but the thermal conductivity thereof is preferablyat least 50 W/m·K, for example, and more preferably at least 100 W/m·K,and even more preferably at least 200 W/m·K.

As shown in FIG. 12 b, in a more preferable configuration of thereference temperature junction sensor 33, the portion of the thermallyconductive layer 34 that is not in contact with the referencetemperature junction 43 is covered with a non-thermally conductivesubstance 35, so the temperature of the reference temperature junction43 can be transferred more reliably to the reference temperaturejunction sensor 33 without the environmental temperature of the nearbyarea having any effect.

There are no particular restrictions on the material of thenon-thermally conductive substance 35, but the thermal conductivitythereof is preferably no more than 20 W/m·K, for example, and morepreferably no more than 1 W/m·K, and even more preferably no more than0.2 W/m·K.

The reference temperature junction sensor 33 is used instead of theenvironmental temperature sensor 22 in Embodiment 1 above. That is, thevarious temperature information used to carry out the temperaturecompensation step S9 is computed in the temperature informationcomputation step S5 according to the algorithm in FIGS. 1, 6, and 7,just as in Embodiment 1, by using the temperature information measuredby the reference temperature junction sensor 33 as the environmentaltemperature information.

The information about measurements of the analysis object via thetemperature compensation step S9 can be obtained as accurate measurementresults, and the effect of temperature due to measurement conditions canbe kept to a minimum just as in Embodiment 1.

The analysis object measurement method in this embodiment is a methodfor measuring an analysis object in which a specific component in ananalysis object is measured with a biosensor system comprising a holderfor holding the analysis object, an electrode system for measuring theanalysis object, and a thermocouple formed by joining at least twodissimilar substances, said method comprising a specimen measurementstep, a temperature information computation step, and a temperaturecompensation step. In the specimen measurement step, a specificcomponent is measured in a spot of the analysis object that has beenapplied to the holder. In the temperature information computation step,temperature information is acquired using the thermocouple. In thetemperature compensation step, the value measured in the specimenmeasurement step is corrected on the basis of the temperatureinformation.

The measured values in the specimen measurement step include, forexample, concentration or volume, mass, various correction items, and soforth, and the temperature compensation step involves correcting thesemeasured values on the basis of temperature information.

With the above method, the characteristics of a thermocouple areutilized to perform temperature measurement, which allows the measuredvalues for an analysis object to be corrected accurately.

As a result, the effect of temperature due to measurement conditions canbe kept to a minimum, and a specific component in the analysis objectcan be measured accurately.

With the method for measuring an analysis object of this embodiment, thetemperature information computation step has a temperature differencemeasurement step, an environmental temperature measurement step, and ameasuring junction calculation step. The temperature differencemeasurement step involves measuring the temperature difference between ameasuring junction that is one of the junctions of the thermocouple anda reference temperature junction that is the other junction. Theenvironmental temperature measurement step involves measuring thetemperature of the reference temperature junction or its nearby area asa reference temperature/environmental temperature. The measuringjunction calculation step involves computing temperature information forthe measuring junction from the temperature difference informationobtained in the temperature difference measurement step.

Here, the “temperature of the nearby area of the reference temperaturejunction” refers to an area within a range in which there is notemperature difference from the reference temperature junctiontemperature.

Because of the properties of a thermocouple, the thermoelectromotiveforce is usually determined by the temperature difference between twopoints: the measuring junction and the reference temperature junction.Accordingly, no matter where on the thermocouple the temperature istransferred due to another factor, as long as the temperature of thereference temperature junction is measured, the temperature of themeasuring junction can be found from the thermoelectromotive force thatis measured.

Consequently, it is possible to accurately calculate the temperature ofthe measurement region where the measuring junction is disposed. As aresult, it is possible to accurately correct the concentration, forexample, which is one of the measured values for the analysis objectthat is measured at the specimen measurement step.

With the method for measuring an analysis object of this embodiment, theenvironmental temperature measurement step and the temperaturedifference measurement step are performed in parallel with the specimenmeasurement step.

The reason the temperature change can be measured in parallel with thespecimen measurement step in the environmental temperature measurementstep and the temperature difference measurement step here is thatneither the thermocouple or the mechanism that measures theenvironmental temperature is affected by the measurement of a specimen,and is also related to the fast response of a thermocouple.

Consequently, the change in temperature during measurement due to allinternal and external factors that affect the temperature of themeasurement region can be detected. Accordingly, the peak temperaturecan also be detected from the pattern of change, and this affords moreaccurate temperature compensation of the analysis object.

With the method for measuring an analysis object of this embodiment, theenvironmental temperature measurement step and the temperaturedifference measurement step involve clocking from a point in time whenmeasurement preparations are complete, or from the point when thespecimen measurement step was started until a predetermined length oftime has elapsed.

Consequently, data for just the length of time necessary for temperaturecompensation can be efficiently extracted. Alternatively, if thereaction system has been thoroughly inspected, just the temperature at apredetermined timing may be measured.

As a result, by measuring for just the required length of time or at therequired timing, the information, power consumption, and steps entailedby measuring the temperature of an analysis object can be reduced.Meanwhile, more accurately temperature compensation can be performed byacquiring temperature information beyond the measurement time for theanalysis object.

With the method for measuring an analysis object of this embodiment, thetemperature compensation step includes an environmental temperaturecompensation step of correcting the measured value on the basis of theenvironmental temperature measured in the environmental temperaturemeasurement step.

This makes it possible to accommodate situations in which temperaturecompensation can be performed more accurately by correcting the measuredvalue on the basis of the environmental temperature, rather than thetemperature of the measuring junction.

With the method for measuring an analysis object of this embodiment, theenvironmental temperature compensation step involves correcting themeasured value on the basis of a correction table containing correctionamounts corresponding to the environmental temperature.

Consequently, it is possible to correct the measured value easily on thebasis of the environmental temperature.

With the method for measuring an analysis object of this embodiment, thetemperature compensation step further includes a measuring junctiontemperature compensation step of correcting the measured value on thebasis of the measuring junction temperature information calculated inthe measuring junction temperature calculation step.

Consequently, even if the temperature of the analysis object duringmeasurement is different from the environmental temperature when thecalibration line was set, the measured value can be corrected on thebasis of the measuring junction temperature information calculated inthe measuring junction temperature calculation step. Thus, situationscan be accommodated in which temperature compensation can be performedmore accurately by correcting the measured value on the basis of themeasuring junction temperature, rather than the environmentaltemperature.

With the method for measuring an analysis object of this embodiment, themeasuring junction temperature compensation step involves correcting thepattern of change of the measuring junction temperature, or the peaktemperature, or the temperature at a predetermined point in time.

Consequently, correction is possible according to the ideal format oftemperature information for the targeted analysis object.

With the method for measuring an analysis object of this embodiment, themeasuring junction temperature compensation step involves correcting themeasured value on the basis of a correction table containing correctionamounts corresponding to the measuring junction temperature information.

Consequently, it is possible to correct the measured value easily on thebasis of the measuring junction temperature.

With the method for measuring an analysis object of this embodiment, thetemperature compensation step further includes a correction itemtemperature compensation step of correcting each correction itemaffected by temperature out of the various correction items obtained inthe specimen measurement step, on the basis of the environmentaltemperature and/or the measuring junction temperature.

The “various correction items” referred to here are elements other thantemperature for correcting the measured values of the analysis object,and include hematocrit value correction, correction of interferingsubstances, etc.

Consequently, just as with the analysis object, the various correctionitems can also be corrected for the effect of environmental temperatureor the temperature of the measurement region, or both, so the measuredvalues for the analysis object can be acquired more accurately.

With the method for measuring an analysis object of this embodiment, thecorrection item temperature compensation step involves correcting thevarious correction items on the basis of a correction table containingcorrection amounts corresponding to the environmental temperature and/orthe measuring junction temperature.

Consequently, it is possible to correct the measured value easily on thebasis of the environmental temperature and the measuring junctiontemperature information.

With the method for measuring an analysis object of this embodiment, thetemperature calculated in the measuring junction temperature calculationstep is used as the temperature inside the holder for holding theanalysis object.

Consequently, it is possible to measure the raw temperature of theanalysis object being measured, and the measured values can be correctedmore accurately.

With the method for measuring an analysis object of this embodiment, thetemperature calculated in the measuring junction temperature calculationstep is used as the temperature of the measurement component serving asthe measurement region between the electrodes in the measurement of theanalysis object.

Consequently, it is possible to measure the raw temperature of theregion of the analysis object that is actually being measured, and themeasured values can be corrected more accurately.

With the method for measuring an analysis object of this embodiment, thetemperature compensation step is performed when the environmentaltemperature or the temperature difference calculated in the temperaturedifference measurement step indicates a specific value.

Consequently, the above-mentioned correction can be performed only onmeasured values that are expected to have low accuracy.

The biosensor of this embodiment comprises a holder, an electrodesystem, and a thermocouple. The holder holds an analysis object. Theelectrode system measures the analysis object. The thermocouple isformed by joining at least two dissimilar substances.

Consequently, it is possible to acquire temperature information andmeasure an analysis object with a biosensor.

With the biosensor of this embodiment, the junction of dissimilarsubstances is a measuring junction of a thermocouple. The measuringjunction is disposed inside the holder for holding the analysis object.

Consequently, it is possible to measure the temperature of an analysisobject directly. Making a correction on the basis of a temperatureacquired in this way keeps the effect of temperature due to measurementconditions to a minimum, and allows an accurate measured value to beprovided for a specific component of the analysis object.

With the biosensor of this embodiment, the junction of dissimilarsubstances is a measuring junction of a thermocouple. The measuringjunction is disposed near the holder.

Consequently, when the measurement of the analysis object and theacquisition of temperature information by the thermocouple has anadverse effect on each other or on one or the other, the temperature ismeasured at as close as possible to the temperature of the measurementcomponent. Making a correction on the basis of a temperature acquired inthis way keeps to a minimum the effect of temperature due to themeasurement conditions, and allows an accurate measured value to beprovided for a specific component of the analysis object.

With the biosensor of this embodiment, the measuring junction isdisposed upstream from the electrode system with respect to the flow ofthe placed drop of analysis object.

Consequently, the wiring of the thermocouple and the electrode systemcan be facilitated.

With the biosensor of this embodiment, both ends that are part of thethermocouple are in locations that come into contact withthermocouple-use connection terminals provided to a measurement devicethat measures the analysis object drop placed in the holder, in mountingto this measurement device.

Consequently, when the biosensor is actually mounted to a measurementdevice that is the key component that performs measurement andcomputation, an environment can be provided that takes advantage of theinherent performance of the thermocouple and the measurement device.

With the biosensor of this embodiment, the substance that makes up thethermocouple is composed of either a metal, an alloy, or asemiconductor, or a combination of these.

Consequently, it is possible to select the material as dictated by theapplication conditions.

With the biosensor of this embodiment, the holder has a cavitystructure, and is formed by affixing a first substrate, a secondsubstrate, and a third substrate together so that the analysis objectwill be supplied by capillary action.

Consequently, capillary action can be utilized to guide the analysisobject into the measurement component. Thus, various measurements of theintroduced analysis object can be performed in the measurementcomponent.

With the biosensor of this embodiment, the holder is formed by affixingtwo substrates together by the three-dimensional molding of thesubstrates.

Consequently, the sensor is made up of fewer members, and themanufacturing processing can be simplified.

With the biosensor of this embodiment, the electrode system and thethermocouple are both provided on the same substrate.

Consequently, in producing and machining the electrode system andthermocouple, they can be machined simultaneously on a single substrate,or can be centralized thereon.

With the biosensor of this embodiment, the electrode system has itselectrodes formed on mutually opposing substrates, with one electrodesystem and the thermocouple both formed on the same substrate.

Consequently, the electrode system and the thermocouple are disposedover a wider area, which affords greater latitude in wiring to suit theintended application.

With the biosensor of this embodiment, the electrode system and thethermocouple are formed on mutually opposing substrates or substrateside faces.

Consequently, the electrode system and the thermocouple are independentof each other, which affords even greater latitude in wiring, and makesit possible, for example, to dispose the measuring junction directlyover the measurement component.

With the biosensor of this embodiment, one of the substances that formthe thermocouple utilizes the wiring of the electrode system, or is madeof the same material as the electrode system.

This imparts the function of a thermocouple to the electrode used formeasuring a specific component, or to the electrode used for measuringcorrection items.

Consequently, whereas three different materials (the electrode material,the thermocouple material 1, and the thermocouple material 2) wouldotherwise be necessary, using an electrode/thermocouple material 1 and athermocouple material 2 reduces the number of manufacturing steps andalso lowers costs.

With the biosensor of this embodiment, the thermocouple and theelectrode system are formed on the substrates by sputtering, vapordeposition, or printing.

Consequently, it is possible to use the manufacturing method that isbest suited to producing an electrode system and a thermocouple.

With the biosensor of this embodiment, the electrode system is such thatan electroconductive layer is formed over all or part of at least oneface among the first substrate, the second substrate, and the thirdsubstrate, and slits are provided to form an electrode pattern.

Consequently, the electrode pattern can be easily modified by changingthe drawing model as necessary.

With the biosensor of this embodiment, the electrode system is such thatan electrode pattern is formed by masking over all or part of at leastone face among the first substrate, the second substrate, and the thirdsubstrate.

Consequently, the electrode system can be produced at just the requiredplace, so when a noble metal or the like is used for the electrodesystem, the amount in which it is used can be reduced. Also, thematerial of the electrode system can be recovered from the masked memberby using one of the various methods that have already been developed.

With the biosensor of this embodiment, the electrode is such that apattern is formed by masking over all or part of at least one face amongthe first substrate, the second substrate, and the third substrate.

Consequently, it is possible to produce the thermocouple withoutoverlapping the electrode system or any place other than the measuringjunction.

With the biosensor of this embodiment, all or part of the surface of theholder is covered with a surfactant.

Consequently, a hydrophilic side wall is formed, so the analysis objectcan be introduced more efficiently into the holder (the cavity, etc.).

With the biosensor of this embodiment, the electrode system has at leasta working electrode and a counter electrode.

Consequently, various targeted components can be quantified by applyingan appropriate voltage to the working electrode and the counterelectrode and detecting the redox current produced from the targetedcomponents.

With the biosensor of this embodiment, a measurement reagent foroxidizing or reducing a specific target component is provided to theholder.

Consequently, the targeted components can be quantified by applyingvoltage to the counter electrode and the working electrode used formeasuring the specific components (part of the electrode system),detecting the redox current produced from the targeted components and ameasurement-use reagent, and converting the current value into atargeted component content.

The biosensor of this embodiment is used disposably.

Consequently, even when an infectious analysis object is measured,measurements can be made any number of times with a single measurementdevice by replacing just the biosensor each time. This also lowers thecost borne by the user.

The measurement device of this embodiment comprises a holder for holdingan analysis object, an electrode system for measuring the analysisobject, and a thermocouple formed by joining at least two substances andthat outputs a temperature difference as a thermoelectromotive force, ora sensor holder to which can hold a removable biosensor comprising apart thereof. The sensor holder has measurement-use connection terminalsthat are in contact with the electrode system in the biosensor and areused to take off signals required for measuring the specific component,and thermocouple-use connection terminals that are in contact with thethermocouple in the biosensor and are used to take off thethermoelectromotive force signals.

Consequently, it is possible to perform the electrochemical operationrequired for various measurements, such as electrically connecting thethermocouple and the electrode system on the biosensor, applyingvoltage, and reading the current value.

With the measurement device of this embodiment, the thermocouple-useconnection terminal is made of the same material as the thermocouple inthe biosensor with which it is in contact, or is an compensating leadmaterial corresponding to the material of the thermocouple.

Consequently, the reference temperature junction of the thermocouple canbe extended to the thermocouple-use connection terminals.

With the measurement device of this embodiment, the thermocouple-useconnection terminals are both made of the same material, which isdifferent from the materials constituting the thermocouple.

Consequently, the ends of the thermocouple on the biosensor can betreated as the reference temperature junction of the thermocouple.

With the measurement device of this embodiment, the surface of thethermocouple-use connection terminals has undergone metal plating.

Consequently, ends that function to hold the biosensor will haveimproved durability with respect to the plugging and unplugging of thebiosensor.

The measurement device of this embodiment comprises a thermocoupleprovided to the biosensor, and a second thermocouple that forms abiosensor/measurement device integrated thermocouple via thethermocouple-use connection terminals.

Consequently, the reference temperature junction of the thermocouple isextended to the ends of the second thermocouple (second wiring) insidethe measurement device, and it is possible to measure the temperaturedifference between the inside of the measurement device and themeasuring junction on the biosensor.

With the measurement device of this embodiment, the ends of the secondthermocouple disposed in the measurement device are disposed as close aspossible.

Consequently, the temperature difference between the ends of the secondthermocouple serving as the reference temperature junction can beeliminated as much as possible.

With the measurement device of this embodiment, the ends of the secondthermocouple are a reference temperature junction of a thermocouple thatis integrated with the biosensor, and the measurement device comprisesan environmental temperature sensor for acquiring the referencetemperature/environmental temperature of the reference temperaturejunction or of the integrated thermocouple that is nearby.

Consequently, the reference temperature/environmental temperature can bemeasured at the reference temperature junction of an integratedthermocouple.

As a result, it is possible to calculate the temperature of themeasuring junction according to the temperature difference informationof the thermocouple.

With the measurement device of this embodiment, the environmentaltemperature sensor individually has a first temperature sensor foracquiring the reference temperature of the integrated thermocouple, anda second temperature sensor for acquiring the environmental temperatureof the measurement device.

Consequently, by individually measuring the reference temperature andthe environmental temperature it is possible to acquire suitabletemperature information for each.

The measurement device of this embodiment comprises a function ofmeasuring the temperature of the measuring junction, integrally with thethermocouple provided to the biosensor.

Consequently, the effect of temperature due to measurement conditionscan be kept to a minimum by means of the temperature information of themeasurement component, and a specific component of the analysis objectcan be accurately measured.

With the measurement device of this embodiment, the thermocouple-useconnection terminals are such that the ends of the thermocouple on thebiosensor are disposed as close as possible.

Consequently, the temperature difference between the ends can be kept toa minimum even with a configuration in which the thermocouple ends onthe biosensor serve as the reference temperature junction of thethermocouple.

The measurement device of this embodiment further comprises a referencetemperature junction temperature sensor that is disposed in contact withthe ends of the reference temperature junction of the thermocoupledisposed in the biosensor, or nearby these ends, and is for acquiringthe reference temperature/environmental temperature of the thermocouple.

Consequently, the reference temperature junction temperature can bemeasured at the reference temperature junction of the thermocouple onthe biosensor.

As a result, it is possible to calculate the temperature of themeasuring junction according to the temperature difference informationof the thermocouple.

With the measurement device of this embodiment, the referencetemperature junction temperature sensor individually has a thirdtemperature sensor for acquiring the reference temperature of thethermocouple disposed in the biosensor, and a fourth temperature sensorfor acquiring the environmental temperature of the measurement device.

Consequently, by individually measuring the reference temperature andthe environmental temperature it is possible to acquire suitabletemperature information for each.

The measurement device of this embodiment further comprises theabove-mentioned biosensor.

Consequently, a thermocouple is formed by a biosensor and a measurementdevice, and the thermocouple characteristics discussed above can beutilized to directly measure the temperature of an analysis object.

As a result, the effect of temperature due to measurement conditions canbe kept to a minimum, and a specific component of the analysis objectcan be accurately measured.

The measurement device of this embodiment further comprises anarithmetic processing unit for calculating temperature information atthe measuring junction, which is one of the junctions of thethermocouple formed in the biosensor, using as a reference the referencetemperature/environmental temperature or the reference temperature.

Here, the arithmetic processing unit calculates temperature informationat the measuring junction on the basis of the temperature of thereference temperature junction measured by the reference temperaturejunction sensor, or the temperature of the reference temperaturejunction measured by the environmental temperature sensor.

With the measurement device of this embodiment, the arithmeticprocessing unit corrects the measured value that is the result ofmeasuring the specific component in the drop of analysis object placedin the holder, on the basis of the reference temperature/environmentaltemperature or the reference temperature.

The measured value referred to here includes, for example, concentrationor volume, mass, various correction items, and so forth.

Consequently, even if the temperature when the analysis object ismeasured is different from the temperature when the calibration line forcalculating the measured value was set, the measured value can still becorrected on the basis of the temperature measured by the environmentaltemperature sensor or the reference temperature junction sensor.

With the measurement device of this embodiment, the arithmeticprocessing unit corrects the measured value that is the result ofmeasuring the specific component in the drop of analysis object placedin the holder, on the basis of the temperature information at themeasuring junction.

The measured value referred to here includes, for example, concentrationor volume, mass, various correction items, and so forth.

Consequently, even if the temperature when the analysis object ismeasured is different from the temperature when the calibration line forcalculating the measured value was set, the measured value can still becorrected on the basis of the temperature information for the measuringjunction

With the measurement device of this embodiment, the arithmeticprocessing unit performs temperature correction for the variouscorrection items with respect to the result of measuring the drop ofanalysis object placed in the holder, on the basis of the referencetemperature/environmental temperature or the reference temperature,and/or the temperature information at the measuring junction, andcorrects the measured value on the basis of these temperature-correctedcorrection items.

The various correction items referred to here are elements forcorrecting measured values, such as concentration, and include all itemsthat are affected by temperature, such as hematocrit value correction,correction of interfering substances, etc.

Consequently, the effect of temperature can be excluded for the variouscorrection items that affect the measured values, so the measured valuesfor the analysis object can be corrected more effectively, and thesemeasured values can be more accurate.

The measurement device of this embodiment further comprises acurrent/voltage conversion circuit, an amplifier circuit, an A/Dconverter circuit, and a memory device. The current/voltage conversioncircuit converts the current values measured by the electrode system andthe environmental temperature sensor or the reference temperaturejunction sensor into voltage. The amplifier circuit amplifies thethermoelectromotive force in the biosensor. The A/D converter circuitconverts the voltage converted by the current/voltage conversion circuitor the amplifier circuit into a digital signal. The memory devicerecords the various measured values and the various temperatureinformation converted into a digital signal by the A/D convertercircuit. The arithmetic processing unit computes the various measuredvalues and the various temperature information from the digital signals,and corrects the various measured values using the various temperatureinformation according to various conditions.

With the measurement device of this embodiment, the memory device has acorrection table used by the arithmetic processing unit for correctingthe various correction items or the measured values corresponding to theenvironmental temperature or the reference temperature and the measuringjunction temperature.

Consequently, the measured values for the various correction items canbe corrected easily by using this correction table.

With the present invention, the temperature inside a holder that holdsan analysis object can be measured directly, so more accuratetemperature compensation of the analysis object is possible, and aspecific component of the analysis object can be measured accurately.

The invention claimed is:
 1. A measurement device, comprising: a sensorholder; a biosensor, the biosensor being removable connected to thesensor holder; a cavity in the biosensor for holding an analysis object;an electrode system in the biosensor for measuring the analysis object;and a thermocouple or a part thereof formed by joining at least twosubstances and that outputs a temperature difference as athermoelectromotive force, wherein the sensor holder has measurement-useconnection terminals that are in contact with the electrode system inthe biosensor and are used for communicating signals required formeasuring the specific component, and thermocouple-use connectionterminals that are in contact with the thermocouple in the biosensor andare used for communicating the thermoelectromotive force signals.
 2. Themeasurement device according to claim 1, wherein the thermocouple-useconnection terminal is made of the same material as the thermocouple inthe biosensor with which it is in contact, or is made of an acompensating lead wire corresponding to the material of thethermocouple.
 3. The measurement device according to claim 1, whereinthe thermocouple-use connection terminals are both made of the samematerial, which is different from the materials constituting thethermocouple.
 4. The measurement device according to claim 1, whereinthe surface of the thermocouple-use connection terminals has undergonemetal plating.
 5. The measurement device according to claim 1, whereinthe thermocouple provided to the biosensor, and a second thermocoupleform a biosensor/measurement device integrated thermocouple via thethermocouple-use connection terminals.
 6. The measurement deviceaccording to claim 5, wherein the ends of the second thermocoupledisposed in the measurement device are disposed as close as possible. 7.The measurement device according to claim 6, wherein the ends of thesecond thermocouple are a reference temperature junction of thethermocouple, which is integrated with the biosensor, and comprise anenvironmental temperature sensor to acquire the referencetemperature/environmental temperature disposed on or near the referencetemperature junction of the integrated thermocouple.
 8. The measurementdevice according to claim 7, wherein the environmental temperaturesensor individually has a first temperature sensor for acquiring thereference temperature of the integrated thermocouple, and a secondtemperature sensor for acquiring the environmental temperature of themeasurement device.
 9. The measurement device according to claim 1,wherein the thermocouple, which is provided on the biosensor, isconfigured to measure integrally the temperature of the measuringjunction.
 10. The measurement device according to claim 9, wherein thethermocouple-use connection terminals are such that the ends of thethermocouple on the biosensor are disposed as close as possible.
 11. Themeasurement device according to claim 10, further comprising a referencetemperature junction temperature sensor that is disposed in contact withthe ends of the reference temperature junction of the thermocoupledisposed in the biosensor, or nearby these ends, and is for acquiringthe reference temperature/environmental temperature of the thermocouple.12. The measurement device according to claim 11, wherein the referencetemperature junction temperature sensor individually has a thirdtemperature sensor for acquiring the reference temperature of thethermocouple disposed in the biosensor, and a fourth temperature sensorfor acquiring the environmental temperature of the measurement device.13. The measurement device according to claim 8, wherein the biosensorcomprises: the cavity for holding an analysis object; the electrodesystem for measuring the analysis object; and the thermocouple formed byjoining the at least two dissimilar substances.
 14. The measurementdevice according to claim 1, further comprising an arithmetic processingunit for calculating temperature information at the measuring junction,which is one of the junctions of the thermocouple formed in thebiosensor, using as a reference the reference temperature/environmentaltemperature or the reference temperature.
 15. The measurement deviceaccording to claim 14, wherein the arithmetic processing unit correctsthe measured value that is the result of measuring the specificcomponent in the drop of analysis object placed in the cavity, on thebasis of the reference temperature/environmental temperature or thereference temperature.
 16. The measurement device according to claim 14,wherein the arithmetic processing unit corrects the measured value thatis the result of measuring the specific component in the drop ofanalysis object placed in the cavity, on the basis of the temperatureinformation at the measuring junction.
 17. The measurement deviceaccording to claim 15, wherein the arithmetic processing unit correctsthe various correction items with respect to the result of measuring inthe drop of analysis object placed in the cavity, on the basis of thereference temperature/environmental temperature or the referencetemperature, and/or the temperature information at the measuringjunction, and corrects the measured value on the basis of thesetemperature-corrected correction items.
 18. The measurement deviceaccording to claim 14, further comprising a current/voltage conversioncircuit for converting the current values measured by the electrodesystem and the environmental temperature sensor or the referencetemperature junction sensor into voltage; an amplifier circuit foramplifying the thermoelectromotive force; an A/D converter circuit forconverting the voltage converted by the current/voltage conversioncircuit or the amplifier circuit into a digital signal; and a memorydevice for recording the various measured values and the varioustemperature information converted into a digital signal by the A/Dconverter circuit, wherein the arithmetic processing unit computes thevarious measured values and the various temperature information from thedigital signals, and corrects the various measured values using thevarious temperature information according to various conditions.
 19. Themeasurement device according to claim 18, wherein the memory device hasa correction table used by the arithmetic processing unit for correctingthe various correction items or the measured values corresponding to theenvironmental temperature or the reference temperature and the measuringjunction temperature.